Differential effect of psoralidin in enhancing apoptosis of colon cancer cells via nuclear factor-κB and B-cell lymphoma-2/B-cell lymphoma-2-associated X protein signaling pathways

Abstract

Abstract. Worldwide, colon cancer is the third most common cancer in terms of incidence, following lung and breast cancer. Resistance to psoralidin frequently occurs following its use as an anticancer treatment. However, the mechanisms underlying the effects of psoralidin on colon cancer, remain to be elucidated. Hence, the present study investigated the anticancer effects and potential mechanism of action of psoralidin on SW480 human colon cancer cells. In the present study, an MTT assay was performed to measure the viability of SW480 cells. Additionally, an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit, DAPI staining assay and caspase-3 colorimetric assay kits were used to analyze the cellular apoptosis of SW480 cells. The nuclear factor-κB (NF-κB) p65 activity and B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) protein expression of SW480 cells was detected using NF-κB colorimetric assay kits and western blot analysis, respectively. Bcl-2 inhibitor ABT-737 was added to SW480 cells and the subsequent effects and mechanism of action of psoralidin on SW480 colon cancer cells was studied. In the present study, psoralidin reduced SW480 cell viability and enhanced the cellular apoptosis of SW480 cells in a dose-dependent manner. Caspase-3 activity of SW480 cells was increased following treatment with psoralidin. Additionally, psoralidin was able to reduce the NF-κB p65 activity of SW480 cells. Furthermore, psoralidin was able to reduce Bcl-2 protein expression and increase Bax protein expression in SW480 cells. Notably, Bcl-2 inhibitor was observed to enhance the effects of psoralidin on SW480 cells.The results of the present study suggest that psoralidin may be a candidate drug for the treatment of colon cancer by inhibition of the NF-κB and Bcl-2/Bax signaling pathways.

Psoralidin prevents caffeine-induced damage and abnormal differentiation of bone marrow mesenchymal stem cells via the classical estrogen receptor pathway

“…Therefore, we aimed to investigate whether PL could reverse excessive caffeine-caused injury in vitro and in vivo and, if so, to elucidate the underlying mechanisms. Documented studies have demonstrated that PL regulates several extracellular signaling pathways, which include the protein kinase B/glycogen synthase kinase 3β/β-catenin signaling pathway, the nuclear factor-kappa B (NF-κB) and phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway, and the NF-κB and B-cell lymphoma-2 (Bcl-2)/ Bcl-2 associated X protein (Bax) signaling pathway (16,29,30). Previous studies have demonstrated that PL can inhibit the formation of adipocytes by modulating the classical and membrane ER pathways (16).…”

A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes

“…Psoralidin has also shown promising results in combating breast, colon, prostate and liver cancer by activating oxidative stress, promoting DNA damage via NADPH oxidase 4 (NOX4)-mediated ROS production, decreasing the cell viability and inducing apoptosis (Ren et al 2016 ) (Jin et al 2016 ) (Bin et al 2019 ) (Szliszka et al 2011 ). Despite its broad activity, human clinical trials with psoralidin are scarce with only the effect of this molecule on dermatological conditions being previously investigated (Gopal et al 2001 ).…”

Pharmacological Activities of Psoralidin: A Comprehensive Review of the Molecular Mechanisms of Action

“…PSO promotes cellular apoptosis and inhibits the cancer cells proliferation in prostate cancer (Szliszka et al, 2011;Das et al, 2014); breast cancer (Dwarampudi et al, 2012); liver cancer (Luo et al, 2013); colon cancer (Jin et al, 2016a); esophagal carcinoma (Jin et al, 2016b), or modulate the autophagy in the lung (Hao et al, 2014;Xin et al, 2019).…”